Department of Medicine, Division of Gastroenterology
Digestive System | Endocrine System Diseases | Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases | Surgical Procedures, Operative
Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.
GLP-1, bariatric surgery, enteroendocrine cells, gut hormones, intestinal transit, mass spectrometry, peptidomics, transcriptomics
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Copyright 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
Cell Rep. 2019 Feb 5;26(6):1399-1408.e6. doi: 10.1016/j.celrep.2019.01.047. Link to article on publisher's site
Larraufie P, Roberts GP, McGavigan AK, Kay RG, Li JH, Leiter AB, Melvin A, Biggs EK, Ravn P, Davy K, Hornigold DC, Yeo GS, Hardwick RH, Reimann F, Gribble FM. (2019). Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2019.01.047. Retrieved from https://escholarship.umassmed.edu/oapubs/3770
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Digestive System Commons, Endocrine System Diseases Commons, Endocrinology Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Nutritional and Metabolic Diseases Commons, Surgical Procedures, Operative Commons